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A comparative pharmacodynamic study of ticagrelor versus clopidogrel and ticagrelor in patients undergoing primary
Benjamin Hibbert1, Ronnen Maze1, Ali Pourdjabbar1
1Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Insights
Pretreating with clopidogrel before ticagrelor in primary percutaneous coronary intervention (PPCI) patients enhances platelet inhibition. This combination therapy leads to faster and stronger antiplatelet effects compared to ticagrelor alone.
Area of Science:
- Cardiology
- Pharmacology
- Interventional Cardiology
Background:
- Ticagrelor is superior to clopidogrel for reducing cardiovascular events in primary percutaneous coronary intervention (PPCI).
- The impact of prior clopidogrel administration on ticagrelor's pharmacodynamics in PPCI patients requires evaluation.
Purpose of the Study:
- To assess the pharmacodynamic effects of ticagrelor when administered after clopidogrel pretreatment in PPCI patients.
- To compare platelet reactivity in patients pretreated with clopidogrel versus thienopyridine-naive patients receiving ticagrelor.
Main Methods:
- Platelet reactivity was measured using the VerifyNow P2Y12 assay.
- Measurements were taken at multiple time points up to 48 hours post-ticagrelor bolus.
- Two groups were studied: clopidogrel + ticagrelor (C+T) and thienopyridine-naive ticagrelor (T).
Main Results:
- The C+T group more frequently achieved the primary endpoint (PRU<208 at 2 hours) than the T group (76.0% vs. 44.4%, p=0.026).
- Clopidogrel pretreatment significantly reduced high platelet reactivity at 1, 4, and 6 hours.
- Lower platelet reactivity units (PRUs) were observed in the C+T group from 2 to 48 hours.
Conclusions:
- Ticagrelor following clopidogrel pretreatment in PPCI patients leads to more rapid and profound platelet inhibition.
- A positive pharmacodynamic interaction between clopidogrel and ticagrelor was demonstrated.
- Further research is necessary to confirm if this enhanced inhibition reduces clinical events.
Background:
In patients undergoing primary percutaneous coronary intervention (PPCI) ticagrelor is superior to clopidogrel in reducing cardiovascular events. This study sought to evaluate the effect of clopidogrel pretreatment on the pharmacodynamics of ticagrelor in patients undergoing PPCI.
Methods:
We measured platelet reactivity using the VerifyNow P2Y12 assay at baseline, 1, 2, 4, 6, 12, 24, and 48 hours following ticagrelor bolus in patients previously loaded with clopidogrel (C+T) and in thienopyridine-naive patients (T) referred to our centre for PPCI.
Results:
In total, 52 consecutive eligible patients with ST-elevation myocardial infarction (STEMI) were enrolled (27 C+T and 25 T). Baseline characteristics and mean baseline platelet reactivity units (PRUs) were similar between the groups. The primary endpoint, the proportion of patients achieving a PRU<208 at 2 hours, was more frequently achieved in the C+T group compared to T treatment (76.0% vs 44.4%, p= 0.026). Notably, C+T therapy resulted in fewer patients with high platelet reactivity at 1 hour (56.0% vs. 14.8%), 4 hours (100.0% vs. 61.5%) and 6 hours (100.0% vs. 64%, p<0.01 for all comparisons). Furthermore, C+T therapy was associated with lower PRU values from 2 to 48 hours.
Conclusions:
In patients referred for PPCI, ticagrelor bolus following clopidogrel resulted in more rapid and profound platelet inhibition, demonstrating a positive pharmacodynamic interaction. Further study is needed to determine if this pharmacodynamic effect translates into reduced clinical events.
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